Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
A Phase II, Multicenter, Two-cohort Study of Oral MET Inhibitor Capmatinib in Chinese Adult Patients With EGFR Wild-type (wt), ALK Rearrangement Negative, MET Exon 14 Skipping Mutations, Advanced Non-small Cell Lung Cancer (NSCLC) Who Are Treatment Naive or Failed One or Two Prior Lines of Systemic Therapy
ClinicalTrials.gov Identifier: NCT04677595
Novartis Reference Number: CINC280A2204
Last Update: Jan 30, 2023
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.
The purpose of the study is to learn whether the study treatment (capmatinib), which already shows efficacy and safety in non-Chinese patients, could help Chinese patients with controlling their lung cancer in a safe way. Participants will have a type of lung cancer called non-small cell lung lancer (NSCLC), with a specific alteration in a part of their DNA (called mutation) of the MET gene, within a specific part of this gene called exon 14.
Participants who have advanced (or metastatic) non-small cell lung cancer with specific mutations in the MET gene but without mutations in the EGFR or ALK genes, who are aged 18 years or older will be enrolled in this study.
The study drug, capmatinib (also known as INC280), is an oral drug that is called a 'targeted' medicine, which means it targets particular processes that may not be working properly in cancer cells (called dysregulation). The dysregulation of the MET signaling in cancer cells of patients with NSCLC is believed to make the cancer worse. Capmatinib has been shown to selectively block the effects of the MET gene and therefore may help in keeping the disease under control, stopping cancer cells from growing.
Key Inclusion Criteria:
Chinese adult ≥ 18 years old at the time of informed consent
Histologically confirmed stage IIIB, IIIC or IV NSCLC at the time of study entry, not amenable to curative surgery or radiation or multi-modality therapy (according to staging definition in CSCO guidelines for primary lung cancer, 2019).
Histologically or cytologically confirmed diagnosis of NSCLC that is:
EGFR wt: The EGFR wt status assessed as part of standard of care (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations)
AND ALK rearrangement negative: assessed as part of standard of care by validated test
Cohort 1: Treatment naive participants with MET mutations, or Cohort 2: Pre-treated participants with MET mutations
Cohort 1: participants must not have received any systemic therapy for advanced/metastatic disease (stage IIIB, IIIC or IV NSCLC). Neo-adjuvant and adjuvant systemic therapies will not count as one prior line of treatment if relapse occurred > 12 months from the end of the neo-adjuvant or adjuvant systemic therapy.
Cohort 2: participants must have failed one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB, IIIC or IV NSCLC).
At least one measurable lesion according to RECIST v1.1.
Adequate organ function
ECOG performance status (PS) ≤1
Key Exclusion Criteria:
Prior treatment with any MET inhibitor or HGF-targeting therapy.
Known druggable molecular alterations (such as ROS1 translocation or BRAF mutation, etc.) which might be a candidate for alternative targeted therapies as applicable per local regulations and treatment guidelines.
Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
Presence or history of interstitial lung disease or interstitial pneumonitis, including, clinically significant radiation pneumonitis affecting activities of daily living or requiring therapeutic intervention.
Substance abuse, active infection (including active hepatitis B and C, participants whose disease is controlled under antiviral therapy are eligible, and human immunodeficiency virus (HIV) history positive) or other severe, acute, or chronic medical or psychotic conditions or laboratory abnormalities that in the opinion of the investigator may increase the risk associated with study participation, or that may interfere with the interpretation of study results.
Other protocol-defined inclusion/exclusion criteria may apply.